Asthma is a prevalent pulmonary disease that affects more than 300 million people worldwide and imposes a substantial economic burden. While medication can effectively control symptoms in some patients, severe asthma attacks, driven by airway inflammation induced by environmental and infectious exposures, continue to be a major cause of asthma-related mortality. Heterogeneous phenotypes of asthma include type 2 (T2) and non-T2 asthma. Non-T2 asthma is often observed in patients with severe and/or steroid-resistant asthma. This review covers the molecular mechanisms, clinical phenotypes, causes and promising treatments of non-T2 severe asthma. Specifically, we discuss the signalling pathways for non-T2 asthma including the activation of inflammasomes, interferon responses and interleukin-17 pathways, and their contributions to the subtypes, progression and severity of non-T2 asthma. Understanding the molecular mechanisms and genetic determinants underlying non-T2 asthma could form the basis for precision medicine in severe asthma treatment.

哮喘是一种流行的肺部疾病，影响着全世界超过 3 亿人，并造成巨大的经济负担。虽然药物可以有效控制某些患者的症状，但由环境和感染性暴露引起的气道炎症引起的严重哮喘发作仍然是哮喘相关死亡的主要原因。哮喘的异质表型包括 2 型 (T2) 和非 T2 哮喘。非 T2 哮喘常见于患有严重和/或类固醇抵抗性哮喘的患者。这篇综述涵盖了非 T2 严重哮喘的分子机制、临床表型、病因和有希望的治疗方法。具体来说，我们讨论了非 T2 哮喘的信号传导途径，包括炎症小体的激活、干扰素反应和白细胞介素 17 途径，以及它们对非 T2 哮喘亚型、进展和严重程度的贡献。了解非 T2 哮喘的分子机制和遗传决定因素可以为严重哮喘治疗的精准医学奠定基础。